Systems and methods for temperature correction in test strips for enzyme detection

ABSTRACT

A system for detection of an analyte includes a lateral flow test strip, including a stripe for reacting with an analyte. The system further includes a meter including and executing instructions for reading the lateral flow test strip and determining a level of the analyte. In the system, the level of the analyte determined and adjusted according to an ambient temperature.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims the benefit of Provisional Application No.62/100,015 filed on Jan. 30, 2015, titled “Systems And Methods ForTemperature Correction In Test Strips For Enzyme Detection,” the entiredisclosure of which is hereby incorporated by reference.

BACKGROUND

Vertical flow and lateral flow test strips are unique and innovativemediums providing for point-of-care testing of blood analytes. Whilethis technology can approach the accuracy provided by laboratorytechniques, there are many peculiarities related to these test stripsthat make their operation, construction, use, and calibration difficult.

Temperature is one factor that can affect the accuracy of vertical andlateral flow test strips. Typically, vertical flow test strips includemultiple layers that isolate portions of the sample so that they may bereacted and measured. In the case of analytes like cholesterol and thefractions of cholesterol, the layers may include a hematocrit separationlayer, an analyte isolation layer which may isolate certain lipids fromother lipids, and a reaction layer. The reaction layer typically relieson an enzyme that reacts with the total or isolated lipids in thesample. The reactivity and efficiency of enzymes at creating color froma sample may be affected by temperature.

Similarly, lateral flow test strips may isolate analytes from otherparts of a sample by flowing the sample across a lateral medium.Typically, lateral flow test strips include stripes or reaction areas onthe lateral flow test strip. These stripes change color in response tothe presence of an analyte. These stripes include an antibody thatreacts with the analyte to be tested for. Competitive type assays andsandwich type assays are common in lateral flow test strips. In moreadvanced lateral flow test strips, the color change of the stripe may bemeasured using a light source and an optical sensor. Lateral flow teststrips are more often used to test for enzymes. As noted above, theactivity of enzymes may be affected by temperature.

BRIEF SUMMARY

In one embodiment, a system for detection of an analyte includes alateral flow test strip, including a stripe for reacting with ananalyte. The system further includes a meter including and executinginstructions for reading the lateral flow test strip and determining alevel of the analyte. In the system, the level of the analyte determinedis adjusted according an ambient temperature. Optionally, theinstructions include an algorithm for correlating a characteristic ofthe lateral flow test strip to the level of the analyte. Alternatively,the characteristic is color. Optionally, the meter includes athermometer, the thermometer operable for detecting the ambienttemperature. In one alternative, the analyte is an enzyme. In anotheralternative, the enzyme is A1C. Optionally, the algorithm is based on acalibration for 25° C., and the characteristic is adjusted based on thedifference in the ambient temperature from the calibration.Alternatively, the stripe includes antibodies that react to the analyte.

In one embodiment, a chip for use with a lateral flow test strip, thelateral flow test strip including a stripe for reacting with an analyte,a meter including and executing instructions for reading the lateralflow test strip and determining a level of the analyte, includes anon-transitory computer medium readable by the meter, the non-transitorycomputer medium including instructions for determining the level of theanalyte adjusted according to ambient temperature. Optionally, theinstructions include an algorithm for correlating a characteristic ofthe lateral flow test strip to the level of the analyte. Alternatively,the characteristic is color. Optionally, the meter includes athermometer, the thermometer operable for detecting the ambienttemperature. In one alternative, the analyte is an enzyme.

In one embodiment, a method of determining an analyte level includesproviding a lateral flow test strip, including a stripe for reactingwith an analyte; and a meter including and executing instructions forreading the lateral flow test strip and determining a level of theanalyte. The method further includes placing a sample on the lateralflow test strip and reading the lateral flow test strip with the meter.The method further includes adjusting the level of the analytedetermined by the meter based on the ambient temperature. Optionally,the instructions include an algorithm for correlating a characteristicof the lateral flow test strip to the level of the analyte.Alternatively, the characteristic is color. In one alternative, themeter includes a thermometer, the thermometer operable for detecting theambient temperature. Optionally, the analyte is an enzyme.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows one embodiment of a color adjustment algorithm based on theambient temperature.

DETAILED DESCRIPTION

Certain terminology is used herein for convenience only and is not to betaken as a limitation on the embodiments of the systems, compositions,and methods of temperature correction in test strips for enzymedetection.

In some embodiments, a lateral flow test strip is used in conjunctionwith a meter to test for the concentration of an analyte. In manyembodiments, the analyte is an enzyme. Examples of enzymes include A1C(glycated hemoglobin) or other enzymes that can bind with antibodies.The antibodies may be located in a stripe on the lateral flow teststrips. Either a competitive or sandwich type assay may be used.

An issue is that the enzyme activity at different temperatures may belessened or increased. Therefore, the amount of color change may beincreased or lessened depending on the type of assay used. This isbecause the enzyme may not react as quickly at lower temperatures. Inthe case of a lateral flow test strip, where a meter is used to read thestrip and calculate a level of analyte in the sample, the meter mayinclude a light source and a sensor. The sensor detects thereflectivity, color change, fluorescence, or other feature of thestripe. This detected level is converted via an algorithm in the meterto a level of analyte in the sample. In some configurations, thealgorithm may be stored on an insertable chip or similar item.Therefore, particular test strips may be provided with particular chipsincluding algorithms for the test strips.

Therefore, in some embodiments, the algorithm for calculatingconcentration of an analyte from the color change may be modified inrelation to the temperature detected by the meter. To accommodate thischange, the meter may include a temperature sensor to detect ambienttemperature and provide the proper calibration to the meter.

In many embodiments, enzymatic activity doubles about every 10° C. Thatmeans that, under typical ambient conditions, there can be twice theamount of color produced during an end product measurement by the exactsame amount of enzyme and thus can be reported relative between 1× and2× the actual amount. Typical ambient conditions may range from 15° C.to 30° C.

Most analytical systems have temperature controls that heat the entiresystem to 37° C. (body temperature) to avoid issues with temperature.However, in the context of a lateral flow test strip such temperaturecontrols may not be feasible or economical.

Accordingly, an algorithm based on the graph below may be used to adjustthe relative color (fluorescence, reflectivity, or other feature)detected by the meter. FIG. 1 shows one embodiment of a color adjustmentalgorithm based on the ambient temperature. The Y-axis shows therelative color detected by the meter. The X-axis shows the time. Thevarious color data points are representative of the anticipateddifference in enzyme activity based on the temperature of the sample. Asis visible in the FIGURE, the trend lines for the color change has agreater slope at higher temperatures and a lesser slope at lowertemperatures.

Accordingly, the same amount of enzyme will produce these differentcolors based upon temperature.

The existing algorithm for the conversion of a measured color change toan amount of analyte in the sample may be modified according to thetemperature. The algorithm assumes curve fitting to the referenceanalyzer at 25° C. (yellow), then use the temperature taken to adjust upor down based upon a comparison of slopes and/or the sin angle functionfor the algorithm. The actual algorithm for calculation of temperatureadjustment may include results of enzyme activities at many additionallevels or alternatively may interpolate between known levels. Activitytrends are believed to be consistent across normally encounteredtemperature ranges.

In many embodiments, the correction algorithm is provided in the form ofa chip, such as a MEMo Chip. The chip may include a bias function. Thebias function may operate by storing an ambient temperature value at themoment the first test runs after the system is powered up. In someembodiments, the ambient temperature value is not updated until the nextpowerup. The chip may include a memory location programmed to theambient temperature at the time the temperature curve was set in qualitycontrol operations.

As an example, the chip additionally may be programmed with a percentvalue. A value of 100% results in +/−1 mg/dL per Degree C of delta fromthe curve set temperature. A value of 50% results in +/−0.5 mg/dL perDegree C of delta from the curve set temperature. A value of 150%results in +/−1.5 mg/dL per Degree C of delta from the curve settemperature. The change in temperature between the startup temperatureand the temperature at the end of the test is calculated using, forexample, the equation:

CurveSetTemperature−StartupTemperature=dT.

This simply means the curve was set at a temperature 1.80° C. less thanthe temperature of the current test run. The reflectivity of the sampleis measured, and this is converted into a concentration of analyte inthe sample (in mg/dL, for example). This formula applies the correctionfactor from the chip to calculate the corrected value:

K=UncorrectedK+(dT*(long)wCorrectionFactor/100).

This is an example of an algorithm that may be applied. Similaralgorithms may be used for temperature corrections in lipids andcorrections for hematocrits. In the case of hematocrits, instead ofmeasuring a starting temperature, a standard hematocrit level is assumedand calculated from that standard value based on a measured andcalculated hematocrit value.

While specific embodiments have been described in detail in theforegoing detailed description and illustrated in the accompanyingFIGURE, it will be appreciated by those skilled in the art that variousmodifications and alternatives to those details could be developed inlight of the overall teachings of the disclosure and the broad inventiveconcepts thereof. It is understood, therefore, that the scope of thisdisclosure is not limited to the particular examples and implementationsdisclosed herein but is intended to cover modifications within thespirit and scope thereof as defined by the appended claims and any andall equivalents thereof. Note that, although particular embodiments areshown, features of each attachment may be interchanged betweenembodiments.

What is claimed as new and desired to be protected by Letters Patent ofthe United States is:
 1. A system for detection of an analyte,comprising: a lateral flow test strip, including a stripe for reactingwith an analyte; and a meter including and executing instructions forreading the lateral flow test strip and determining a level of theanalyte, wherein the level of the analyte determined is adjustedaccording to an ambient temperature.
 2. The system of claim 1, whereinthe instructions include an algorithm for correlating a characteristicof the lateral flow test strip to the level of the analyte.
 3. Thesystem of claim 2, wherein the characteristic is color.
 4. The system ofclaim 3, wherein the meter includes a thermometer, the thermometeroperable for detecting the ambient temperature.
 5. The system of claim1, wherein the analyte is an enzyme.
 6. The system of claim 5, whereinthe enzyme is A1C.
 7. The system of claim 4, wherein the algorithm isbased on a calibration for 25° C. and the characteristic is adjustedbased on the difference in the ambient temperature from the calibration.8. The system of claim 1, wherein the stripe includes antibodies for theanalyte.
 9. A chip for use with a lateral flow test strip, the lateralflow test strip including a stripe for reacting with an analyte, a meterincluding and executing instructions for reading the lateral flow teststrip and determining a level of the analyte, the chip comprising: anon-transitory computer medium readable by the meter, the non-transitorycomputer medium including instructions for determining the level of theanalyte adjusted according to ambient temperature.
 10. The chip of claim9, wherein the instructions include an algorithm for correlating acharacteristic of the lateral flow test strip to the level of theanalyte.
 11. The chip of claim 10, wherein the characteristic is color.12. The chip of claim 11, wherein the meter includes a thermometer, thethermometer operable for detecting the ambient temperature.
 13. The chipof claim 9, wherein the analyte is an enzyme.
 14. A method ofdetermining an analyte level, the method comprising: providing a lateralflow test strip, including a stripe for reacting with an analyte; and ameter including and executing instructions for reading the lateral flowtest strip and determining a level of the analyte; placing a sample onthe lateral flow test strip; reading the lateral flow test strip withthe meter; and adjusting the level of the analyte determined by themeter based on the ambient temperature.
 15. The method of claim 14,wherein the instructions include an algorithm for correlating acharacteristic of the lateral flow test strip to the level of theanalyte.
 16. The method of claim 15, wherein the characteristic iscolor.
 17. The method of claim 16, wherein the meter includes athermometer, the thermometer operable for detecting the ambienttemperature.
 18. The method of claim 14, wherein the analyte is anenzyme.